FOXO4-DRI
Also known as: FOX04-DRI, FOXO4 D-Retro-Inverso, Proxofim
Popular For
Senescent cell clearance, tissue rejuvenation, aging
Key Facts: FOXO4-DRI
- Category
- Anti-Aging
- FDA Status
- Not FDA Approved
- Clinical Status
- Preclinical - Extensive animal research, Phase 1 trials planned
- Administration
- Subcutaneous injection (community), IV/IP in animal studies
- Typical Dose
- 2-10 mg every other day for 3 doses (one cycle)
- Frequency
- 3 doses every other day, 1-3 cycles per year
- Evidence Level
- Animal Studies
- Duration
- 1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly
Mechanism of Action
FOXO4-DRI is a D-retro-inverso peptide that interferes with the binding between FOXO4 and p53 proteins. In senescent cells, FOXO4 binds to p53 to prevent apoptosis, allowing these dysfunctional cells to persist. FOXO4-DRI competes for this binding, releasing p53 to trigger apoptosis specifically in senescent cells while sparing healthy cells.
Research Summary
Landmark 2017 Cell study demonstrated that FOXO4-DRI restored fitness, fur density, and renal function in aged mice. Studies show improved kidney tubular cell markers, better urea/creatinine metrics, and reduced SASP (senescence-associated secretory phenotype) cytokines. A 2025 Nature Communications study provided detailed structural insights into the FOXO4-p53 interaction mechanism. Cleara Biotech is developing FOXO4-DRI for conditions including kidney disease, COPD, and osteoarthritis.
Dosing Information
Note: Animal study doses may not translate directly to humans.
Typical Dosingⓘ
Community experience
2-10 mg every other day for 3 doses (one cycle)
2-25 mg per injection, 6-75 mg total per cycle
3 doses every other day, 1-3 cycles per year
Senolytic peptide - used in short intermittent cycles, not daily. Mouse studies used 5 mg/kg x3 doses (translates to ~25 mg/dose for 60kg human). Biohacker protocols vary: some use 2-3 mg every other day for 6 days, others use higher 10-25 mg doses for 3 injections. Lower-dose protocols (300-500 mcg daily for weeks) also reported. Subcutaneous injection most common. Side effects may include injection site reactions, fatigue, muscle soreness, nausea.
Research Dosingⓘ
Scientific studies
Doses from animal studies and biohacker community protocols
Doses from Studies
5 mg/kg in mice x3 doses
Preclinical Research - Cell 2017 - Restoration of tissue homeostasis ↗
2-3 mg every other day for 6 days
Community Protocol - Biohacker protocols (Ben Greenfield et al.) ↗
Duration
1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly
Administration
Subcutaneous injection (community), IV/IP in animal studies
Timing & Administration
Best Time to Take
Per research protocol
Intermittent dosing (e.g., 3 doses over 1 week, then break)
Food Recommendation
With or without food
Why This Timing?
FOXO4-DRI is typically administered in intermittent treatment cycles rather than daily dosing. The peptide triggers apoptosis in senescent cells, which then need time for clearance and tissue regeneration.
Possible Side Effects
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Generally well-tolerated in animal studies
- ●Injection site reactions (burning, itching)
- ●Fatigue
- ●Muscle soreness
- ●Nausea
- ●No significant effects on platelet levels or blood values in animal studies
- ●No observed damage to non-proliferative tissues (heart)
- ●Limited human safety data
- ●Theoretical concern: could affect beneficial senescent cells (wound healing, tumor suppression)
References
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Educational Information Only
This information is provided for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare providers before making any decisions about peptides or other substances. The protocols listed reflect doses observed in research studies, not recommendations.